Why Biology May Differ Between Races
Imagine a type of breast cancer so aggressive that it lacks the three receptors targeted by most effective treatments—estrogen, progesterone, and HER-2. This is triple-negative breast cancer (TNBC), accounting for 15-20% of all breast cancer cases but responsible for a disproportionate number of breast cancer deaths.
Survivin is something of a biological paradox. During fetal development, it's essential for healthy growth, but it largely disappears in most adult tissues.
In cancer cells, however, survivin makes a dramatic comeback, playing a dual role in both blocking cell death and regulating cell division 2 .
Key Fact: Survivin is overexpressed in nearly every human cancer but barely detectable in normal tissues, making it an ideal therapeutic target 2 .
When researchers analyzed data from The Cancer Genome Atlas (TCGA), a startling pattern emerged. While levels of survivin itself were similar between African American (AA) and European American (EA) patients with TNBC, the kinases that activate survivin told a different story.
Both PLK1 and AURKB showed significantly higher expression levels in African American patients compared to their European American counterparts 1 .
| Kinase | Statistical Significance | Interpretation |
|---|---|---|
| PLK1 | P = 0.026 | Significant |
| AURKB | P = 0.045 | Significant |
P-values < 0.05 indicate statistical significance unlikely due to chance 1 .
The team studied six different TNBC cell lines—three derived from African American patients and three from European American patients 1 .
Using small interfering RNAs (siRNAs), the researchers selectively turned off the survivin gene in these cell lines to observe the effects 1 .
They measured cell proliferation rates using BrdU incorporation, a method that identifies dividing cells 1 .
The team implanted human TNBC tumors into mouse models and treated them with kinase inhibitors volasertib (against PLK1) and barasertib (against AURKB) 1 .
Finally, they examined human TNBC tissue samples from 148 patients (108 African American and 40 European American) to confirm their findings in real patient specimens 1 .
| Cell Type | Proliferation Impact | Cell Cycle Progression |
|---|---|---|
| African American TNBC cells | Significant attenuation | Substantially impaired |
| European American TNBC cells | Minimal effect | Minimal impact |
| Tumor Origin | PLK1 Inhibition (Volasertib) | AURKB Inhibition (Barasertib) |
|---|---|---|
| African American TNBC tumors | Significant growth inhibition | Significant growth inhibition |
| European American TNBC tumors | Minimal effect | Minimal effect |
Modern cancer biology relies on sophisticated tools to unravel complex cellular processes.
| Reagent/Technique | Function in Research | Specific Application in This Study |
|---|---|---|
| Small interfering RNA (siRNA) | Gene silencing | Selectively turning off survivin gene to study its function |
| BrdU cell proliferation assay | Measuring cell division | Identifying actively dividing cells after survivin manipulation |
| Volasertib & Barasertib | Kinase inhibitors | Blocking PLK1 and AURKB activity in animal models |
| Immunoblotting | Protein detection | Measuring levels of survivin, p-survivin, and kinases |
| Immunohistochemistry | Visualizing proteins in tissues | Examining protein levels and localization in patient samples |
| Flow cytometry | Cell cycle analysis | Determining proportion of cells in different cell cycle phases |
The most exciting implication of this research is the potential for personalized cancer therapies specifically for African American patients with TNBC.
The striking finding that volasertib and barasertib significantly inhibited growth in AA TNBC tumors but not EA tumors suggests that kinase inhibitors may be particularly effective for this patient population 1 .
This approach represents a shift from one-size-fits-all cancer treatments toward precision medicine that considers both the cancer type and the patient's biological background.
This research highlights a crucial evolution in our understanding of cancer biology.
The racial disparity in TNBC outcomes couldn't be fully explained by differences in gene expression alone, since survivin levels were similar across racial groups 1 .
The key difference lay not in the amount of survivin protein, but in its activation state through phosphorylation. This underscores the importance of looking beyond genetics to the complex world of post-translational modifications 1 5 .
The discovery that PLK1 and AURKB collude with survivin to drive aggressive tumor proliferation in African American TNBC represents more than just a scientific breakthrough—it offers hope for addressing a persistent health disparity.
"Our findings suggest that pharmacological inhibition of PLK1 and AURKB may be a viable therapeutic option for Black women with TNBC" 5 .
By understanding the unique biology of TNBC in different racial groups, we can move toward truly personalized medicine that delivers the right treatment to the right patient at the right time.
This research opens a new avenue for investigating the biological basis of racial disparities not just in breast cancer, but potentially across multiple cancer types.
While much work remains to translate these findings into clinical treatments, this research represents an important step toward equitable cancer care—where a patient's racial background informs their treatment strategy, potentially narrowing the survival gap that has plagued oncology for decades.